FUS (fusion involved in t(12;16) in malignant liposarcoma)

Identity

Other names	TLS (translocated in liposarcoma)
HGNC	FUS
Location	16p11.2
Location_base_pair	Starts at 31098954 and ends at 31110600 bp from pter ( according to hg18-Mar_2006).

DNA/RNA

Description	The gene has 15 exons, and the total genomic sequence spanning the FUS gene is approx. 12 Kb.
Transcription	Transcript lenght: 1,9 Kb. There are two isoforms produced by an alternative splicing that involved the exon 4a (145 bp) or the exon 4b (142 bp).

Protein

Description	526 amino acids (isoform with the exon 4a) or 525 aa (isoform with the exon 4b), 68 Kda. The protein contains different domains: a N-terminal SYQG-rich region; a RGG-rich region; a RNA binding domain; a RGG-rich region; a Cys2/Cys2-zinc finger motif and; a C-terminal RGG-rich region.
Expression	FUS is expressed in a housekeeping pattern.
Localisation	Nuclear, although FUS shuttles from the nucleus to the cytoplasm in a large complex that contains mRNA and hnRNPs.
Function	FUS is a RNA-binding protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. FUS seems to have a function as a heterogeneous ribonuclear protein (hnRNP)-like chaperone of RNA. In addition, it has been suggested that FUS might have a role in the BCR/ABL-mediated leukemogenesis.
Homology	FUS forms a sub-family of RNA binding proteins with EWS and RBP56/hTAFII68. FUS has homologous in mouse (fus), rat (pigpen) and Drosophila (Cabeza/SARFH).

Mutations

Germinal

In the mouse, germline mutation in the fus gene produces male sterility, sensitivity to radiation, defective B-lymphocyte development and activation, chromosomal instability and perinatal death.

Implicated in

Note	The FUS gene is implicated in several chromosomal translocations associated to both solid tumors and leukemias. The result of these chromosomal translocations are gene fusions. FUS contributes to these fusions with its N-terminal part, just before the RNA-binding domain. This domain confers to the fusion protein a transcriptional activation domain. These fusion genes generated as a result of chromosomal rearragements are used to monitor diagnosis and treatment.
Entity	t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/ATF-1.
Disease	Angiomatoid fibrous histiocytoma (AFH).
Hybrid/Mutated Gene	FUS was interrupted at codon 175 (exon 5) and fused to codon 110 (exon 5) of ATF-1, resulting in an in-frame junction with a glycine to valine (GGT to GTT) transition.
Entity	t(7;16)(q33;p11) chromosomal translocation. It produces the fusion protein FUS/CREB3L2 (also known as BBF2H7).
Disease	Low grade fibromyxoid sarcoma (LGFMS).
Hybrid/Mutated Gene	The breakpoints in the fusion transcripts are produced between the exons 6 or 7 of FUS and the exon 5 of CREB3L2.
Entity	t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3 (also known as CHOP).
Disease	Myxoid liposarcoma (MLS).
Hybrid/Mutated Gene	9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3.
Oncogenesis	The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter.
Entity	t(16;21)(p11;q22) chromosomal translocation. It produces the fusion protein FUS/ERG.
Disease	Acute myeloid leukemia (AML).
Hybrid/Mutated Gene	The junction of both genes is produced between the exons 6 or 7 of FUS and the exon 9 of ERG,or between the exon 8 of FUS and the exon 7 of ERG.

Breakpoints

External links

	Nomenclature
HGNC	FUS   4010
Entrez_Gene	FUS  2521  fusion (involved in t(12;16) in malignant liposarcoma)
	Cards
Atlas	FUSID44
GeneCards	FUS
Ensembl	FUS [Search_View]   ENSG00000089280 [Gene_View]  FUS [Vega]
Genatlas	FUS
GeneLynx	FUS
eGenome	FUS
euGene	2521
	Genomic and cartography
GoldenPath	FUS  -  16p11.2   chr16:31098954-31110600 +  16p11.2   [Description]    (hg18-Mar_2006)
Ensembl	FUS - 16p11.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	FUS
	Gene and transcription
Genbank	AB208902 [ ENTREZ ]
Genbank	AK098774 [ ENTREZ ]
Genbank	AK130774 [ ENTREZ ]
Genbank	AK290936 [ ENTREZ ]
Genbank	AK299129 [ ENTREZ ]
RefSeq	NM_004960 [ SRS ]    NM_004960 [ ENTREZ ]
RefSeq	AC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
RefSeq	AC_000148 [ SRS ]    AC_000148 [ ENTREZ ]
RefSeq	NC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
RefSeq	NT_010393 [ SRS ]    NT_010393 [ ENTREZ ]
RefSeq	NW_001838236 [ SRS ]    NW_001838236 [ ENTREZ ]
RefSeq	NW_926306 [ SRS ]    NW_926306 [ ENTREZ ]
CCDS	FUS CCDS - NCBI
AceView	FUS AceView - NCBI
Unigene	Hs.513522 [ SRS ]    Hs.513522 [ NCBI ]     HS513522 [ spliceNest ]
Fast-db	7666 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P35637 [ SRS]    P35637 [ EXPASY ]     P35637 [ INTERPRO ]     P35637 [ UNIPROT ] P35637 [ VarSplice ]
Prosite	PS50102 RRM [ SRS ]    PS50102 RRM [ Expasy ]
Prosite	PS01358 ZF_RANBP2_1 [ SRS ]    PS01358 ZF_RANBP2_1 [ Expasy ]
Prosite	PS50199 ZF_RANBP2_2 [ SRS ]    PS50199 ZF_RANBP2_2 [ Expasy ]
Interpro	IPR000504 RRM_RNP1 [ SRS ]    IPR000504 RRM_RNP1 [ EBI ]
Interpro	IPR001876 Znf_RanBP2 [ SRS ]    IPR001876 Znf_RanBP2 [ EBI ]
CluSTr	P35637
Pfam	PF00076 RRM_1 [ SRS ]    PF00076 RRM_1 [ Sanger ]    pfam00076 [ NCBI-CDD ]
Pfam	PF00641 zf-RanBP [ SRS ]    PF00641 zf-RanBP [ Sanger ]    pfam00641 [ NCBI-CDD ]
Smart	SM00360 RRM [EMBL]
Smart	SM00547 ZnF_RBZ [EMBL]
Blocks	P35637
HPRD	00660
	Protein Interaction databases
DIP	P35637
IntAct	P35637
	Polymorphism : SNP, mutations, diseases
OMIM	137070    [ map ]
GENECLINICS	137070
SNP	FUS [dbSNP-NCBI]
SNP	NM_004960 [SNP-NCI]
SNP	FUS [GeneSNPs - Utah]  FUS] [HGBASE - SRS]
HAPMAP	FUS [HAPMAP]
COSMIC	FUS [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	FUS [Translocation breakpoints In Cancer]
HGMD	FUS
Genetic Association	FUS
CDC HuGE	FUS
	General knowledge
Family Browser	FUS [UCSC Family Browser]
SOURCE	NM_004960
SMD	Hs.513522
SAGE	Hs.513522
GO	nucleotide binding [Amigo]  nucleotide binding
GO	nuclear mRNA splicing, via spliceosome [Amigo]  nuclear mRNA splicing, via spliceosome
GO	molecular_function [Amigo]  molecular_function
GO	nucleic acid binding [Amigo]  nucleic acid binding
GO	DNA binding [Amigo]  DNA binding
GO	RNA binding [Amigo]  RNA binding
GO	protein binding [Amigo]  protein binding
GO	cellular_component [Amigo]  cellular_component
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	biological_process [Amigo]  biological_process
GO	zinc ion binding [Amigo]  zinc ion binding
GO	metal ion binding [Amigo]  metal ion binding
PubGene	FUS
TreeFam	FUS
CTD	2521 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	FUS Related clones (RZPD - Berlin)
	PubMed
PubMed	42 Pubmed reference(s) in Entrez

Bibliography

Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.

Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR

Nature. 2007 ; 446 (7137) : 758-764.

PMID 17344859

Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).

Aman P, Ron D, Mandahl N, Fioretos T, Heim S, Arheden K, Will��n H, Rydholm A, Mitelman F

Genes, chromosomes & cancer. 1992 ; 5 (4) : 278-285.

PMID 1283316

Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.

Crozat A, Aman P, Mandahl N, Ron D

Nature. 1993 ; 363 (6430) : 640-644.

PMID 8510758

Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.

Rabbitts TH, Forster A, Larson R, Nathan P

Nature genetics. 1993 ; 4 (2) : 175-180.

PMID 7503811

An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation.

Ichikawa H, Shimizu K, Hayashi Y, Ohki M

Cancer research. 1994 ; 54 (11) : 2865-2868.

PMID 8187069

TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain.

Prasad DD, Ouchida M, Lee L, Rao VN, Reddy ES

Oncogene. 1994 ; 9 (12) : 3717-3729.

PMID 7970732

Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities.

S��nchez-Garc��a I, Rabbitts TH

Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (17) : 7869-7873.

PMID 8058726

Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry.

Calvio C, Neubauer G, Mann M, Lamond AI

RNA (New York, N.Y.). 1995 ; 1 (7) : 724-733.

PMID 7585257

Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.

Knight JC, Renwick PJ, Cin PD, Van den Berghe H, Fletcher CD

Cancer research. 1995 ; 55 (1) : 24-27.

PMID 7805034

Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS.

Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, H��glund M, Forster A, Rabbitts TH, Ron D, Mandahl N, Mitelman F

Genomics. 1996 ; 37 (1) : 1-8.

PMID 8921363

Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.

Kong XT, Ida K, Ichikawa H, Shimizu K, Ohki M, Maseki N, Kaneko Y, Sako M, Kobayashi Y, Tojou A, Miura I, Kakuda H, Funabiki T, Horibe K, Hamaguchi H, Akiyama Y, Bessho F, Yanagisawa M, Hayashi Y

Blood. 1997 ; 90 (3) : 1192-1199.

PMID 9242552

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.

Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P

Oncogene. 1997 ; 15 (11) : 1357-1362.

PMID 9315104

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.

Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P

Oncogene. 1997 ; 15 (11) : 1357-1362.

PMID 9315104

TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling.

Zinszner H, Sok J, Immanuel D, Yin Y, Ron D

Journal of cell science. 1997 ; 110 ( Pt 15) : 1741-1750.

PMID 9264461

Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes.

Morohoshi F, Ootsuka Y, Arai K, Ichikawa H, Mitani S, Munakata N, Ohki M

Gene. 1998 ; 221 (2) : 191-198.

PMID 9795213

TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis.

Perrotti D, Bonatti S, Trotta R, Martinez R, Skorski T, Salomoni P, Grassilli E, Lozzo RV, Cooper DR, Calabretta B

The EMBO journal. 1998 ; 17 (15) : 4442-4455.

PMID 9687511

Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS).

Ichikawa H, Shimizu K, Katsu R, Ohki M

Molecular and cellular biology. 1999 ; 19 (11) : 7639-7650.

PMID 10523652

Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death.

Hicks GG, Singh N, Nashabi A, Mai S, Bozek G, Klewes L, Arapovic D, White EK, Koury MJ, Oltz EM, Van Kaer L, Ruley HE

Nature genetics. 2000 ; 24 (2) : 175-179.

PMID 10655065

Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.

Kuroda M, Sok J, Webb L, Baechtold H, Urano F, Yin Y, Chung P, de Rooij DG, Akhmedov A, Ashley T, Ron D

The EMBO journal. 2000 ; 19 (3) : 453-462.

PMID 10654943

A novel FUS/CHOP chimera in myxoid liposarcoma.

Panagopoulos I, Mertens F, Isaksson M, Mandahl N

Biochemical and biophysical research communications. 2000 ; 279 (3) : 838-845.

PMID 11162437

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice.

P��rez-Losada J, Pintado B, Guti��rrez-Ad��n A, Flores T, Ba��ares-Gonz��lez B, del Campo JC, Mart��n-Mart��n JF, Battaner E, S��nchez-Garc��a I

Oncogene. 2000 ; 19 (20) : 2413-2422.

PMID 10828883

Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma.

P��rez-Losada J, S��nchez-Mart��n M, Rodr��guez-Garc��a MA, P��rez-Mancera PA, Pintado B, Flores T, Battaner E, S��nchez-Gar��ia I

Oncogene. 2000 ; 19 (52) : 6015-6022.

PMID 11146553

Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.

Waters BL, Panagopoulos I, Allen EF

Cancer genetics and cytogenetics. 2000 ; 121 (2) : 109-116.

PMID 11063792

Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.

P��rez-Mancera PA, P��rez-Losada J, S��nchez-Mart��n M, Rodr��guez-Garc��a MA, Flores T, Battaner E, Guti��rrez-Ad��n A, Pintado B, S��nchez-Garc��a I

Oncogene. 2002 ; 21 (11) : 1679-1684.

PMID 11896599

Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma.

Storlazzi CT, Mertens F, Nascimento A, Isaksson M, Wejde J, Brosjo O, Mandahl N, Panagopoulos I

Human molecular genetics. 2003 ; 12 (18) : 2349-2358.

PMID 12915480

The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.

Panagopoulos I, Storlazzi CT, Fletcher CD, Fletcher JA, Nascimento A, Domanski HA, Wejde J, Brosj�� O, Rydholm A, Isaksson M, Mandahl N, Mertens F

Genes, chromosomes & cancer. 2004 ; 40 (3) : 218-228.

PMID 15139001

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Contributor(s)

Written	07-2004	PA Pérez-Mancera, Isidro Sánchez-Garía
		Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain

Citation

This paper should be referenced as such :

Pérez-Mancera PA, Sánchez-Garía I . FUS (fusion involved in t(12;16) in malignant liposarcoma). Atlas Genet Cytogenet Oncol Haematol. July 2004 . URL : http://AtlasGeneticsOncology.org/Genes/FUSID44.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sun Nov 9 19:41:04 2008